Non-medical and non-invasive interventions for erectile dysfunction in men with type 2 diabetes mellitus: A scoping review

Background Erectile dysfunction (ED) often affects men with type 2 diabetes mellitus (T2DM) due to microvascular damage. However, medical interventions are not always appropriate. Aim This scoping review aimed to answer the following question: What evidence is available about the effects of non-medical and non-invasive healthcare interventions to improve ED in men with T2DM? Method Potential studies were collected from the Cumulative Index to Nursing and Allied Health Literature via EBSCO, Embase via Ovid, MEDLINE via Ovid, Web of Science, PubMed, ProQuest, and PsycINFO via Ovid. Findings From 2,611 identified titles, 17 studies, including 11 interventional and 6 observational studies, were included. Four main alternatives to medical interventions were identified from the included studies. Amongst these, four studies recommended patient education on lifestyle modification, twelve studies encouraged dietary changes and physical activities, two studies emphasized the use of vacuum erectile device, and three studies suggested the application of low-intensity extracorporeal shockwave therapy by healthcare professionals. Discussion Dietary modification and physical activities were promoted as effective interventions to help maintaining the erectile function in men with T2DM. Several methods of patient education were identified as the approach to facilitate lifestyle modification in men with T2DM-associated ED. The positive outcomes of this review support early ED screening to help preventing T2DM complications such as ED in men. Further, T2DM management is a shared responsibility between the men and healthcare professionals. Despite the success of Vacuum Erectile Device and Low-intensity Extracorporeal Shockwave Therapy in regaining erectile function, further research is needed in this area based on the recommendations of the American Urological Association. Moreover, the health and quality of life of men with T2DM must be improved.


Keywords:
Type-2 diabetes mellitus Erectile dysfunction Patient education Lifestyle Diet modification Physical exercise Therapy Vacuum erectile device Low-intensity extracorporeal shock wave therapy A B S T R A C T Background: Erectile dysfunction (ED) often affects men with type 2 diabetes mellitus (T2DM) due to microvascular damage. However, medical interventions are not always appropriate. Aim: This scoping review aimed to answer the following question: What evidence is available about the effects of non-medical and non-invasive healthcare interventions to improve ED in men with T2DM? Method: Potential studies were collected from the Cumulative Index to Nursing and Allied Health Literature via EBSCO, Embase via Ovid, MEDLINE via Ovid, Web of Science, PubMed, ProQuest, and PsycINFO via Ovid. Findings: From 2,611 identified titles, 17 studies, including 11 interventional and 6 observational studies, were included. Four main alternatives to medical interventions were identified from the included studies. Amongst these, four studies recommended patient education on lifestyle modification, twelve studies encouraged dietary changes and physical activities, two studies emphasized the use of vacuum erectile device, and three studies suggested the application of lowintensity extracorporeal shockwave therapy by healthcare professionals. Discussion: Dietary modification and physical activities were promoted as effective interventions to help maintaining the erectile function in men with T2DM. Several methods of patient education were identified as the approach to facilitate lifestyle modification in men with T2DMassociated ED. The positive outcomes of this review support early ED screening to help preventing T2DM complications such as ED in men. Further, T2DM management is a shared responsibility between the men and healthcare professionals. Despite the success of Vacuum Erectile Device and Low-intensity Extracorporeal Shockwave Therapy in regaining erectile function, further research is needed in this area based on the recommendations of the American Urological Association. Moreover, the health and quality of life of men with T2DM must be improved.

Introduction
Erectile dysfunction (ED), defined as the failure to attain and/or maintain penile erection, is closely associated with type 2 diabetes mellitus (T2DM) [1]. Men with T2DM are at three times higher risk of ED than those without diabetes [2,3]. The persistent hyperglycemia present in T2DM eventually disrupts penile vascularization and damages nerve endings [4]. This leads to fiber and autonomic neuropathies and small artery impairment, all of which contribute to ED [5]. Persistent insulin resistance, on the other hand, is responsible for reduced hypothalamic response to endogenous insulin, thereby causing hypogonadotropic hypogonadism [6,7] and testosterone deficiency in men with T2DM [2]. In addition, the ED can be triggered by anti-hypertensives and anti-depressants that are commonly prescribed to patients with T2DM [8].
Previous studies have shown that ED can develop within the first 5 years following T2DM diagnosis [9]. However, most men were not aware of the issue until the damage had started to affect their personal lives [10]. Thus, the close association between T2DM-associated ED (T2DMED), psychological stress and depression can significantly affect men's quality of life [8,[11][12][13].
In men, T2DMED can cause sexual dissatisfaction and distress [14], unsatisfactory relationships, and marital tension [15,16]. An earlier study found that T2DMED created frustration and anger in men which were directed to their wives [15]. Nevertheless, T2DMED screening is inconsistent, and the provision of support to the men remains a challenging issue [17][18][19].
The use of phosphodiesterase-5 inhibitors (PDE5I) is widely recommended as safe and effective in regaining erectile function [8,20]. However, some men do not respond to PDE5I. Further, invasive treatments may not be desirable nor feasible in some cases. Therefore, this scoping review was conducted to identify non-medical and non-invasive alternatives for maintaining erectile function in men with T2DM.

Design
This scoping review was undertaken to summarize evidence-based alternatives for the non-medical management of T2DMED [21][22][23]. With regard to its nature as a secondary study, this scoping review did not require an ethical approval. The review was conducted in five consecutive stages, as described by Arksey and O'Malley (2005) [21]. These included: (1) identifying the research question, (2) determining relevant studies, (3) selecting relevant studies, (4) charting data, and (5) collating, summarizing, and reporting study results [21]. The conduct of this review was documented and reported based on the Preferred Reporting Items of Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA ScR) checklist (Supplementary File 3) [24].

Establishing the research question
This review aimed to answer the following question: What evidence is available regarding non-medical and non-invasive interventions for managing erectile dysfunction in men with T2DM?

Identifying relevant studies
A set of key terms was developed to maintain research consistency. The terms were cross-checked and expanded using the Medical Subject Headings available in https://meshb.nlm.nih.gov/search for article inclusion (Table 1).
In February 2022, authors evaluated studies published in the following databases: Cumulative Index to Nursing and Allied Health Literature via EBSCO, Embase via Ovid, MEDLINE via Ovid, Web of Science, PubMed, ProQuest, and PsycINFO via Ovid. These databases were selected for their collection of published articles in health and related sciences. The identification of potential additions was made by hand-searching the reference lists of the included studies. However, this review did not consider gray literature for inclusion. The search strings used to identify potential articles for inclusion and the search history is presented in supplementary file 1 and 2.

Table 1
Key words used for searching relevant studies in this review.

Study selection
Eligible studies, including peer-reviewed studies on men diagnosed with T2DMED that were written in English and articles published from January 2002 to February 2022, were assessed for inclusion ( Table 2). All processes in this study selection stage (title, abstract, and full-text review) were independently conducted by two reviewers using an online platform Covidence® (www.covidence. org). The work of this stage was carefully recorded using the 2020's PRISMA ScR flow diagram [24].

Charting the data
The data extracted from the included studies were charted in a table as informed by the Joanna Briggs Institute's Manual for the Conduct of Scoping Reviews [25]. This table provides article details, including name of author(s), publication year, journal volume and issue number, study setting(s), participants/sample details, method(s), intervention(s), and key findings (Table 4).

Collating, summarizing, and reporting data
Extracted data from included studies were coded and analyzed inductively into themes. Based on the accepted approach of scoping reviews, the identified evidence were then summarized without being critically appraised [21].

Included studies
At its final stage, this review included 17 studies eligible for data extraction, with details in the following description and the 2020 PRISMA ScR diagram to illustrate the conducted processes ( Fig. 1).

Title review
The search initially yielded 2,611 titles, which were then exported to Covidence® for duplication removal. This step removed 511 duplicated titles, thereby leaving 2,100 titles for manual abstract review.

Abstract review
Two reviewers individually screened the abstracts of the remaining titles in Covidence®. The third and fourth reviewer were invited to resolve conflicts for final decisions. At this stage, 2,064 records were excluded due to irrelevant topics identified from the abstracts.

Full-text review
At this stage, 36 records were retained for full-text review. Nineteen articles were then excluded based on the inclusion criteria, fulltext availability, and duplication of studies (Fig. 1). The reference lists of the included articles were hand-searched. However, none were eligible for additional inclusion. At the end of this stage, 17 primary studies were included for data extraction (Table 3).

Descriptive findings of the included studies
This scoping review extracted evidence that explored different non-pharmaceutical and non-invasive approaches for regaining or maintaining erectile function in men with T2DM. With regards to the diverse evidence, this review maps the included studies based on Table 2 Criteria for inclusion of published articles.

Participants
Men who were diagnosed with T2DM and experience ED.

Key intervention(s):
Participants in the treatment arm attended weekly group sessions of MEDIC for one month, where clinical pharmacists provided education to intensify behavioural modification (i.e., encourage diet, exercise and disease selfmanagement, tobacco cessation and other comorbid risk reduction) and medication titration followed algorithms to achieve tobacco cessation, glycaemic, blood pressure, and lipid control.

Key finding(s):
Participants who had met goals for both blood pressure and HbA1c experienced the greatest improvement in IIEF-5 (2.2 ± 1.6) followed by participants who met only one of the goals (BP or HbA1c) (− 0.05 ± 0.8), and then by those meeting none of the goals (− 1.5 ± 1.2). Changes in systolic and diastolic BP were still significant predictors of change in IIEF-5 after adjusting for age (P = 0.01 and P = 0.01, respectively) and change in PDE5I use (P = 0.01 and P = 0.01, respectively). Comparative study (independent samples t-test)

Key intervention(s):
All subjects had glycated haemoglobin on diet control or oral hypoglycemic medication. Subjects were randomly assigned to one of two different diets: (continued on next page)

Key intervention(s):
Newly diagnosed patients who had never treated with antidiabetic drugs were randomly assigned to received Mediterranean diet or a low-fat diet, to restrict energy intake to 1800 kcal/day. The Mediterranean diet had the goal of no more than 50% of calories from carbohydrates and no less than 30% calories from fat, with the main source of added fat 30-50 g of olive oil. The lowfat diet had the goal of no more than 30% of calories from fat and no more than 10% of calories from saturated fat.     A statistically significant improvement of mean IIEF-5 scores with respect to baseline was evident in all groups at 4week follow-up. In details, the IIEF-5 scores (mean ± SD) improved by 3.9 ± 1.9 and by 2.9 ± 1.5 in treatment and control group, respectively. At 24-week follow-up, the IIEF-5 (mean ± SD) variations with respect to baseline in treatment and control group were +3.8 ± 2.4 and +1.8 ± 1.7, respectively (P < 0.001 in both groups). These results demonstrate that the combined approach provides advantages in terms of both magnitude of mean IIEF-5 score improvement and durability of results if compared to tadalafil 5 mg once daily alone. Khoo

Key intervention(s):
Subjects in the intervention group were asked to consume 2-3 sachets daily (one at breakfast and lunch and/or dinner) of Kicstart, providing a maximum of 450 kcal of energy, 0.8 g per kg of ideal body weight of high-quality protein, as well as the recommended daily allowances of minerals, vitamins, trace elements, omega-3 and omega − 6 essential fatty acids. One small meal at either lunch or dinner was permitted, consisting of 'noncarbohydrate' vegetables and a small piece of meat, fish or chicken, to achieve a total energy intake of approximately 850-900 kcal per day. Each subject was given the same meal plan with details of specific allowable foods and portions and was able to contact the dietician in between followup visits to answer queries about the (continued on next page) diet.

Key finding(s):
After 8 weeks, the diabetic subjects achieved significant weight loss (9.5 ± 4.8 kg, P < 0.01), reduced waist circumference (12.1 ± 4.8 cm, P < 0.01), and an improvement in insulin sensitivity (percentage change in QUICKI) (9.0 ± 9.1%, P < 0.01) in response to the low-calorie diets. A significant increasement in the mean IIEF-5 score were seen in diabetic subjects (2.1 ± 3.0, P < 0.01) in response to weight loss induced by the LCD. In diabetic men, the absolute increase in the IIEF-5 score was similar to that of the nondiabetic intervention subjects but represented a proportionally greater improvement from baseline. The average SDI scores also increased significantly in the and diabetic subjects (10.4 ± 9.4, P < 0.01).

Origin of studies
Regarding the country of origin, all studies originated from middle-and high-income countries. Up to 47.05% (n = 8) of the included studies were originated from European countries [26,27,29,30,32,35,36,38,43] and a small proportion of the studies (n = 2) were conducted in East Asian countries, including Japan [31] and the People's Republic of China [34] (Fig. 3). This suggests that no studies have been conducted in developing countries.

Study methods
The included studies have a wide variety of methods. In total, 11 were interventional studies, including: five randomized controlled trials (RCTs) [29,30,33,34,42], one non-randomized controlled trial [40], one randomized clinical trial [28], and four pre-and post-intervention studies [26,32,37,43]. The remaining studies were cross-sectionals [31,38,41] and retrospective studies [27,36,39] (Fig. 4). With regards to the length of the conducted trials (Table 4), the shortest study was 1 month [38] and the longest observation was conducted for 8.1 years [30]. Both of these studies advocated a combination of Mediterranean diet and physical exercises to men who were newly diagnosed with T2DM, either as adjunct to oral anti-diabetic therapies [38] or as a single approach for those who had never been prescribed with any medication [30].

Alternatives to non-medical and non-invasive interventions
This review summarizes the alternatives of non-medical and non-invasive treatments identified in the included studies. The studies were then grouped into themes based on the approaches suggested for maintaining and regaining ED in men who were diagnosed with T2DM. The themes included dietary modifications and physical exercises, with additions from a small number of studies that promoted the use of a device or medical assistance to help men achieve erection for sexual penetration, including the use of assistive vacuum erectile device (VED) and low-intensity extracorporeal shockwave therapy (Li-ESWT) ( Table 4). More importantly, all studies highlighted the importance of patient education in facilitating the treatments [39,40,42,43]. However, most of the included studies proposed the interventions in conjunction with hypoglycemic agents [27,28,32,[37][38][39][40]42,43] and/or PDE5I [29,34,36,41]. These interventions were grouped as follows:

Patient education
Different methods of patient education, which can support and facilitate dietary changes and prescribed physical exercises in men, were promoted in four studies [39,40,42,43]. Two studies originating from the USA showed the involvement of multidisciplinary health professionals in patient education [39,42]. This method was used to improve the fundamental awareness of participants on T2DM and associated comorbidities (including ED) and the adoption of healthier lifestyle.
A retrospective analysis of RCTs investigated the significance of a serial multi-professional education referred as Multidisciplinary Education in Diabetes and Intervention for Cardiac Risk Reduction (MEDIC) in empowering affected men to follow the recommended lifestyle modification [39]. The intervention, as described by Martin et al. (2007), was a package of group training sessions that consisted of four weekly sessions (for up to 20 patients) [44]. Each training session comprised of a 90-min education session around T2DM self-management delivered by healthcare professionals (HCP) and a 60-min workshop to assist men in setting goals to achieve behavioral and medication modifications. Based on the MEDIC study, each HCP's roles and participations are explained as follows: 1. Clinical pharmacists explain the medication, risk factors of cardiovascular events, and importance of regular risk monitoring. 2. Nurse educators provide instructions and trainings on using monitoring devices, such as glucometer, pedometer, sphygmomanometer, and other necessary skills for diabetes self-care. 3. Nutritionists are involved in introducing food groups, label reading, and using essential skills to control weight, blood glucose levels, and blood pressure through controlled diet. 4. Social workers as consultants discuss the challenges experienced by men and the strategies that must be used to overcome psychological barriers. 5. Physical therapists are involved to explain safe exercises, skills and tools for heart rate monitoring, and to suggest exercise equipment [44].
Another RCT investigated the effect of intensive lifestyle interventions (ILI) for T2DM that were introduced from a larger and earlier study conducted by The Look AHEAD Research Group [45]. Originally, the ILI was designed as a long-term lifestyle modification tool that includes the following.  However, the included RCT was limited to evaluate outcomes after the first year of the ILI program (phase 1 and 2), particularly to identify its significance on weight loss and erectile function [42]. The dietary modification was designed to restrict calorie intake to 1500 kcal/day for participants weighing up to 113.4 kg and up to 1800 kcal/day for those weighing f more than 113.4 kg [42]. In addition, moderate-intensity exercises, such as brisk walking, was gradually increased up to 175 min per week.
Another study conducted in Turkey investigated the significance of a six-month specific diabetes education program on the erectile function of men diagnosed with T2DM [43]. The education sessions were delivered either fortnightly or monthly to institute dietary modification and adaptation of a proper physical exercise, as complementary to the prescribed anti-hyperglycemic agents (such as metformin, sulfonylureas, and glitazone) and/or other therapies.
Another educational approach was used in a non-RCT study in Australia to assist men with T2DMED in substituting their regular diet by consuming liquid meals [40]. A dietician was involved in establishing a detailed meal plan to identify allowable food and portion, as well as to assist the implementation and monitor the progress at fortnightly basis. The two-month interventions of the trial was principally identified as follows.
1. Two to three sachets of Kicstart (Pharmacy Health Solutions Pty Ltd., Sydney, Australia) to be consumed daily as substitutes to breakfast and lunch or dinner. 2. One small meal comprising "non carbohydrate" vegetables and a small piece of fish or chicken at dinner or lunch can be consumed to achieve a total energy intake of approximately 900 kcal/day.
Another study promoted dietary modification and physical exercise as an effective single approach for men who were newly diagnosed with T2DM and had never been prescribed with antihyperglycemic agents [30]. The study emphasized that a Mediterranean diet is protective against the progression of T2DM and the associated ED (box 1). In addition, the study recommended 30-min of daily aerobic exercise for optimum outcomes [30]. 1. Calorie intake restriction only up to 1800 kcal/day for men and1500 kcal/day for women.

Recommended daily intake:
250-300 g of fruit, 125-150 g of vegetables, 25-50 g of nuts, 400 g of whole grains (such as legumes, rice, maize and wheat), and olive oil.

Assistive device as a treatment modality
This review identified the use of assistive devices that can be prescribed by medical practitioners as second-line alternatives to regain erectile function. VED was identified in two studies as an assistive device that can be prescribed to the men [32,34]. However, different approaches were used in the studies. An RCT originating from China reported improvements in erectile function after 3 months of using the VED following individual tutorial session and an instructional video on how to safely use the device for artificial erection (box 2) [34]. The study reported greater improvement in erectile function in men who used the VED as an addition to PDE5I [34].
In another study,  prescribed the use of VED to men with T2DM who had been unsuccessful with PDE5I [32]. The study involved men who were diagnosed with T2DM less than five years and cautiously excluded those who received anticoagulants or those with cardiovascular risks, penile anomaly, prostate disease, and endocrinological complications. The VED was prescribed as an addition to regular and standard T2DM medical therapies and/or lifestyle modification [32]. Further, the study suggested the minimum use of four times per month and the results to be evaluated after the sixth month.

Energy based therapy
Low-intensity extracorporeal shockwave therapy (Li-ESWT) was identified as a supportive treatment that should be administered by medical specialists [26,33,36]. In a study conducted in Italy,  investigated the use of Li-ESWT as a combination therapy with a 5 mg daily administration of tadalafil in patients with T2DM and ED [36]. The study was designed to evaluate the significance of a six serialtreatments of Li-ESWT with 3-day intervals. The therapy was applied using Omnispec ED1000 (Medispec Ltd., Yehud, Israel) onto the distal, middle, and proximal areas of the penile shaft, and given on both sides of the crura (penile base); with the density of 0.09 mJ/mm 2 and the frequency of 120 shocks/minute for 20 min per session [36].
In the second study conducted in Egypt, a double-blind RCT was undertaken to evaluate the outcomes of Li-ESWT and pelvic floor exercise (PFE) in comparison with PFE in addition to sham therapy [33]. Both the sham and Li-ESWT were delivered twice per week for 3 weeks and were then repeated after a 3 week resting period [33]. Meanwhile, the PFE was prescribed three times per day for 6 weeks [33].
The third study was performed in Turkey to evaluate the outcomes of shockwave therapies in patients who had previously received two courses of Li-ESWT [26]. Each course comprised of five sessions with the average interval of 7 ± 2 day using Linear Renova (Initia Ltd., Petah Tikva), with 20 min of 0.09 mJ/mm 2 intensity on the distal penile shafts. The three studies shared similar criteria, such as excluding men with glycated hemoglobin levels (HbA1C) > 7 mg/mL, hypogonadism, non-adjusted cardiac and antihypertensive medications, penile abnormalities, and history of pelvic surgeries.
Although, some studies reported negative outcomes, for example, Wing et al., reported the worsening ED in 8% of their study sample following lifestyle modifications [42], some argued that this is due to old age, overweight/obesity [42], and later stage T2DM [32,43].

Discussion
This scoping review summarizes evidence extracted from published studies that investigated complementary and alternative interventions to help men with T2DM maintain and/or regain erectile function. Adaptation to healthier lifestyle, including dietary modifications and physical exercises, was the most offered approach identified in the included studies. In addition, a small number of studies introduced VED and Li-ESWT as supportive treatments to regaining erectile function. The findings of this review further supported the need for health professionals to address T2DMED, with regards to the low rates of ED screening in health appointments [8,20,49].
Patient education was identified as the main approach used in promoting lifestyle modification (i.e., dietary change and physical activity) and other measures for improving T2DM management and erectile function [27][28][29][30]37,39,40,42,43]. Some of the included studies have shown that dietary modifications and physical activities (such as aerobic workouts, strengthening exercise, or a combination of the two) are safe and effective therapies for improving general health, diabetes management, and erectile function [27,29,30]. Most studies reported significant outcomes from lifestyle modification as additional therapy to PDE5I. However, regaining erectile function is only possible after correcting body weight (i.e., overweight and obesity) and maintaining the optimum blood sugar level [50]. In addition, the prescribed use of VED and Li-ESWT was reported as potential modalities to help the men in regaining erectile function [26,[32][33][34][35][36].
Studies originated from middle-and high-income countries, such as Italy, the USA, Turkey, China, Egypt, and Australia, showed the magnitude of the issue and the growing awareness of T2DMED in those countries. However, a gap was identified from the absence of such studies in developing countries and the small number of included studies in the present review. Hence, more studies are recommended in future.

Patient education and lifestyle modification
The present review emphasizes the significance of patient education in adopting healthy lifestyle (dietary change and physical activity) for men with T2DM. The promoted lifestyle modifications identified in the studies is effective in preserving erectile function in men newly diagnosed with T2DM. Thus, such approaches should be adopted as early as possible following T2DM diagnosis [51,52], to lower the risk of ED and other related complications.
Patient education has always been recommended as the initial approach for improving T2DM screening uptake and management [53]. Improved knowledge will direct patient awareness on T2DM and increase treatment adherence [54]. The European Association of Urology recommends education as an essential approach that will prevent misleading information, which is the primary cause of mismanagement and further unnecessary burdens, including T2DMED [52,54]. As emphasized by Katana et al. (2008) and Wing et al. (2010), the multidisciplinary involvement of professionals (including medical physicians, dieticians, physical therapists, pharmacists, nurses, and social workers) is significant in patient education and instituting healthier lifestyle to men with T2DMED. Therefore, a collaborative approach should be considered as a way to improve the sexual and general well-being of men with T2DM [39,42]. This approach was recommended by the American Diabetes Association in the 2019 and 2020 Standards of Medical Care in Diabetes [55,56].
Most studies in this review reported improvements in erectile function following lifestyle modification in addition to pharmacological approaches. However, one study revealed that lifestyle modification can be effective as a single intervention to protect the men against ED. Particularly, in individuals who were newly diagnosed with T2DM and had never received anti-diabetic agents [30]. Healthy diet, balanced energy intake, weight loss, improved blood pressure, better glycemic control, and physical conditioning are some of the outcomes that lead to the improved testosterone level and overall erectile function [27,28,30,[37][38][39][40][41][42][43]. Nonetheless, this review identified a small number of cases where the prescribed treatments were not proven to be effective [42,43]. These studies argued that the undesirable results are attributed to old age and the longer duration of poorly managed T2DM [42,43]. Hence, damage had already progressed and irreversibly impacted men who had lived with longer periods of T2DM [51,57]. All these suggest the need for the early diagnosis of T2DM, identification of T2DMED, and initiation of lifestyle modifications [35,58,59]. It also supports the need for interactions between the men and the HCPs to facilitate ED screening and discussion [8,20,49].

Courses of treatment modality
The prescribed use of VED and courses of Li-ESWT are identified as alternative modalities for preserving erectile function in men with T2DM [26,[32][33][34][35]. The VED was suggested as a safe and effective self-performed therapy before considering invasive procedures [34]. In the study,  reported the 85% success rate of VED in helping the men to regain satisfying artificial erection, including in those who were not on pharmacological therapies [32]. The artificial erection was facilitated by the negative pressure created to improve temporary penile blood flow, similar to normal penile erection [34]. However, one should consider the possible issues associated with the device, which include penis base coldness, pain, petechial bleeding, and penile numbness [32,33]. For these reasons, the American Urological Association (AUA) recommended a moderate-level use of VED n (evidence level: grade C) [50]; and suggested medical advice and supervision [32,34].
Unlike the VED, the course of Li-ESWT should only be administered by medical specialists [26,33,36]. Li-ESWT is identified as a supportive therapy to either pelvic floor exercise (Kegel) or daily consumption of PDE5I [26,33,36]. Although the benefits of Li-ESWT remained questionable (evidence level: grade C) [50]. The methods (i.e., VED and Li-ESWT), however, do not improve the underlying pathology (i.e., diabetes mellitus), which is key in managing T2DMED [50,52]. Therefore, the course of either VED or Li-ESWT should be based on a careful consideration [50].

Strengths and limitations
The present review has limitations due to its nature as a secondary study and the quality of the work. First, the evidence identified in published studies cannot draw emerging topics or produce novel findings. Rather, a scoping review is used as a method to

Box 2
Basic principles on the use of VED, as described by  1. Without the constrictor ring, use the battery-operated pump to create an artificial erection. 2. Once the desired state of erection is achieved, maintain the pump for 1-2 min and then release. 3. Repeat the use for at least 30 min per day or use the constrictor ring for coitus. 4. Only use the constrictor ring for 30 min to prevent injury. summarize or map available evidence on a particular topic [21,23]. Second, the limited analysis that focused on managing T2DMED was attributed to small numbers of identified studies that were then included in this review. Therefore, future studies on the topic are recommended to address this gap. For instance, exploration of the factors affecting early diagnosis of T2DMED or treatments offered in healthcare settings. Third, the exclusion of gray literature could have limited the potential reports or other papers that could have provided a valuable information on the topic. However, this review followed rigorous processes, based on a widely accepted framework [21][22][23].

Conclusions
This review summarizes non-medical and non-invasive alternatives for T2DMED. Further, the evidence was extracted from the included studies using a widely accepted framework. Lifestyle modifications including dietary change and physical exercise, either as a single approach or combined with medical therapy, were identified as havingt positive effects against ED in men who were newly diagnosed with T2DM. Patient education is widely offered to facilitate lifestyle modification in men with T2DM.
The positive outcomes of this review support the initiation of ED screening and discussion to lower the risks of future complications of T2DM in men. The application of multidisciplinary approaches in educating patients about managing T2DM requires a collective and shared responsibility among HCPs. In addition, the use of VED and Li-ESWT is offered as an additional alternative to allow satisfactory erection, despite recommendation for further investigation of these treatments. Thus, the findings of this review should be used in future studies that aim to improve the health and quality of life of men with T2DM.

Authors contribution statement
Setho Hadisuyatmana, Sonia Reisenhofer: Conceived and designed the experiments; Performed the experiments; Contributed reagents, materials, analysis tools or data; Analyzed and interpreted the data; Wrote the paper. Ferry Efendi, Michael Bauer: Conceived and designed the experiments; Analyzed and interpreted the data. James Boyd, Gulzar Malik: Analyzed and interpreted the data; Wrote the paper.

Data availability
Data will be made available on request.

Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.